Study to Evaluate the Safety, Tolerability and the Effect of BMS-241027 on Cerebrospinal Fluid Biomarkers in Subjects With Mild Alzheimer's Disease

• Safety assessments: based on frequency of Serious Adverse Events (SAEs), frequency of Adverse events (AEs), discontinuation due to AEs and dose reduction [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
• Biomarker Measures: CSF levels of Tau N-terminal domain fragments [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]

• Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
• Effects of BMS-241027 on cognitive performance using computerized cognitive tests [ Time Frame: Weeks 3, 6 and 9 ] [ Designated as safety issue: No ]
• Effects of BMS-241027 on connectivity MRI [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
• Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
• Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7
• Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
• Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
• Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]
• Effects of BMS-241027 on CSF levels of neurofilaments [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]

• Effects of BMS-241027 on CSF levels of the mid-domain Tau fragment [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
• Effects of BMS-241027 on cognitive performance using computerized cognitive tests [ Time Frame: Weeks 3, 6 and 9 ] [ Designated as safety issue: No ]
• Effects of BMS-241027 on connectivity MRI [ Time Frame: Within the first 70 days after first dose ] [ Designated as safety issue: No ]
• Maximal observed plasma concentration (Cmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter Cmax will be derived from subgroups of subjects at Week 7
• Observed plasma concentration at 24 hours post dose (C24) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter C24 will be derived from subgroups of subjects at Week 7
• Time of maximal observed plasma concentration (Tmax) of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter Tmax will be derived from subgroups of subjects at Week 7
• Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-241027 in subjects with mild Alzheimer's disease [ Time Frame: Weeks 1, 4, and 9 ] [ Designated as safety issue: No ]
  Intensive pharmacokinetic parameter AUC(TAU) will be derived from subgroups of subjects at Week 7
• Safety assessments: based on vital sign measurements, ECGs and clinical laboratory tests [ Time Frame: Within the first 70 day after first dose ] [ Designated as safety issue: Yes ]

The purpose of the study is to evaluate safety and the pharmacodynamic effects of BMS-241027 on cerebrospinal fluid (CSF) Tau, connectivity magnetic resonance imaging (MRI), and computerized cognitive tests in mild Alzheimer's disease (AD) subjects, following 9 weekly intravenous (IV) infusions of BMS-241027

• Drug: BMS-241027
  Intravenous (IV), 0.003 mg/kg, Once Weekly, 9 weeks
• Drug: BMS-241027
  Intravenous (IV), 0.01 mg/kg, Once Weekly, 9 weeks
• Drug: BMS-241027
  Intravenous (IV), 0.03 mg/kg, Once Weekly, 9 weeks
• Drug: Placebo matching BMS-241027
  Intravenous (IV), 0.0 mg/kg, Once Weekly, 9 weeks

• Experimental: Arm 1: BMS-241027 (0.003 mg/kg)
  Intervention: Drug: BMS-241027
• Experimental: Arm 2: BMS-241027 (0.01 mg/kg)
  Intervention: Drug: BMS-241027
• Experimental: Arm 3: BMS-241027 (0.03 mg/kg)
  Intervention: Drug: BMS-241027
• Experimental: Arm 4: Placebo matching BMS-241027
  Intervention: Drug: Placebo matching BMS-241027

Inclusion Criteria:

• Mild AD Subjects meeting National Institute of Neurological Disorders and Stroke - Alzheimer's Disease Related Disorders Association(NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders-Forth Edition, Text Revision (DSM-IV-TR) criteria
• Mini-Mental State Exam (MMSE) Score between 20 & 26 (inclusive)
• CSF consistent with AD pathology
• Screening brain MRI - normal - commensurate with age or demonstrate atrophy consistent with AD diagnosis (dx); reveal no more than mild white matter disease; up to 2 lacunar infarcts acceptable except in anterior thalamus, genu of internal capsule or basal forebrain; reveal no cortical infarcts; reveal no more than 4 microbleeds; reveal no focal asymmetric lobar atrophy or other findings suggesting primary cause of dementia is attributed to a cause other than AD; reveal no macrohemorrhages (>10 mm)
• Subjects must have reliable study partners
• Men and Women of Non Child Bearing Potentia (WONCBP), ages 50-90 years

Exclusion Criteria:

• Subjects with any other medical condition other than mild AD that could explain subjects' memory or cognitive deficits
• Subjects diagnosed with moderate or severe AD per DSM-IV criteria
• Subjects with a history (hx) of stroke
• Subjects with a hx of GI illnesses
• Subjects with Vitamin B12 or folate deficiency
• Subjects with any unstable cardiovascular (CV), pulmonary, Gastrointestinal (GI) or hepatic disease within 30 days prior to screening
• Subjects with active liver dx or history of hepatic intolerance
• Subjects with a Geriatric Depression Scale score of ≥ 6 at screening
• Subjects treated for or have had a diagnosis of schizophrenia
• Subjects treated for or have had a diagnosis of bipolar disease within 3 years prior to screening
• Subjects with a history of generalized peripheral neuropathy